浙江大学学报（医学版）2026，Vol.55Issue(5)：437-448,12.DOI:10.3724/zdxbyxb-2025-0747
补肾益精方改善阿尔茨海默病模型鼠认知功能的机制研究
Mechanism of Bushen Yijing Formula improving cognitive function in Alzheimer's disease model mice
摘要
Abstract
Objective:To explore the mechanism of Bushen Yijing Formula(BSYJF)in the treatment of Alzheimer's disease(AD)through an integrated approach combining transcriptomics,network pharmacology,and molecular docking.Methods:Twelve specific pathogen-free male C57BL/6 mice,aged 6 months,were used in this study.Among them,four wild-type mice served as the normal control group,and eight amyloid precursor protein(APP)/presenilin 1(PS1)double-transgenic mice were randomly divided into a model control group and a BSYJF group,with four mice in each group.Mice in the BSYJF group were orally administered 8.56 mL/kg BSYJF by gavage once daily,while those in the model control and normal control groups received an equal volume of normal saline by gavage.All treatments were continued for 12 consecutive weeks.Cognitive function and hippocampal amyloid β-protein(Aβ)deposition were assessed using behavioral tests and immunohisto-chemistry.Mouse brain tissue samples were subjected to transcriptomic sequencing to identify differentially expressed genes(DEGs).Functional enrichment analyses were performed using Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis(GSEA).In parallel,active compounds of BSYJF were screened via the TCMSP and PubChem databases,and AD-related targets were retrieved from GeneCards and other disease databases.Core targets were identified by intersecting these targets with transcriptomic DEGs.Molecular docking and molecular dynamics simulations were employed to evaluate binding affinity between active compounds and core targets,and quantitative polymerase chain reaction(qPCR)was used to validate expression changes of core target genes.Results:BSYJF treatment improved cognitive function and reduced hippocampal Aβ deposition in APP/PS1 mice.Transcriptomic analysis revealed 73 DEGs between the model and BSYJF groups.GO analysis identified enrichment in 281 biological processes,104 cellular components,and 120 molecular functions.KEGG analysis highlighted 110 pathways,and GSEA supplemented 322 enriched gene sets,many related to the immune system,neurodegenerative diseases,and signaling pathways such as Th17 cell differentiation and NF-κB.Integrated analysis with network pharmacology prioritized 10 core targets.Molecular docking and molecular dynamics simulations indicated strong structural stability and binding affinity of BSYJF bioactive constituents to these core targets.qPCR results confirmed that BSYJF down-regulated the expression of Aurkb,Nr1i3,and Ttk,while upregulating Apob and Ces1d,consistent with the transcriptomic findings.Conclusion:BSYJF may regulate immune-inflammatory responses and alleviate neuronal damage through a multi-component,multi-target,and multi-pathway approach,thereby improving cognitive function in AD model mice.关键词
阿尔茨海默病/补肾益精方/转录组学/网络药理学/认知功能/海马β淀粉样蛋白/APP/PS1小鼠Key words
Alzheimer's disease/Bushen Yijing Formula/Transcriptomics/Network pharmacology/Cognitive function/Hippocampal Aβ/APP/PS1 mice分类
医药卫生引用本文复制引用
张哲祚,李德雨,刘晶,鲁磊,蔡文慧,于顾然..补肾益精方改善阿尔茨海默病模型鼠认知功能的机制研究[J].浙江大学学报（医学版）,2026,55(5):437-448,12.基金项目
国家重点研发计划(2022YFC3501403) （2022YFC3501403）
江苏省院士工作站(BM2024101)This study was supported by National Key R&D Program of China(2022YFC3501403),and Jiangsu Provincial Academician Workstation(BM2024101) （BM2024101）
